Basic Research for AIDS control A01 ; Host factors necessary for HIV-1 replication

艾滋病控制基础研究A01；

• 批准号: 10180101
• 负责人: KOYANAGI Yoshio
• 金额: $ 118.46万
• 依托单位: TOHOKU UNIVERSITY (2000-2001)The University of Tokyo (1998-1999)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas (A)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10180101/
• 关键词: HIV-1; AIDS; CD4(+) T cell; NF-kappaB; Chemokine receptor; Retrovirus; Integration; Nuclear export; ゲノム; TAT; インテグレース; REV; 核内因子; HIV-1; gp41; Nef; 阻害剤; RANTES; サル細胞; SIV; SDFA; CD26; 糖鎖; 逆転写; アクセサリー蛋白; サブタイプEゲノム

Koyanagi reported that TRAIL but not FasL was involved in the apoptotic death of CD4(+) T cells in infected individuals using SCID-PBL mouse system. Furthermore, they showed that TRAIL was also involved in the neuronal cell death in a murine model of HIV central nervous system infection. Shioda identified a deletion mutation in the CCR5 gene specifically seen in Asian population and showed that this mutation affected the surface trafficking of CCR5, resulting in the low sensitivity to HIV-1 infection in the affected individuals. Okamoto identified the host factors essential for viral transcription. One was AES/TLE, as a co-repressor of NF-kappaB p65. Another was FUS/TLS, as a co-activator of NF-kappaB. Masuda found a novel nuclear import signal located in HIV-1 integrase. Shida reported that CRAM1 is necessary for the oligomerization of Rev protein and that human CRAM1 also functioned even in murine cells.

Koyanagi等利用SCID-PBL小鼠系统报道，TRAIL而非FasL参与了感染个体中CD 4（+）T细胞的凋亡性死亡。此外，他们还发现TRAIL也参与了HIV中枢神经系统感染小鼠模型中的神经元细胞死亡。Shioda在亚洲人群中发现了CCR 5基因的缺失突变，并表明该突变影响了CCR 5的表面运输，导致受影响个体对HIV-1感染的敏感性降低。冈本确定了病毒转录所必需的宿主因子。一种是AES/TLE，作为NF-κ B p65的共阻遏物。另一种是FUS/TLS，作为NF-κ B的共激活剂。增田在HIV-1整合酶中发现了一种新的核输入信号。Shida报道CRAM 1对于Rev蛋白的寡聚化是必需的，并且人CRAM 1甚至在鼠细胞中也起作用。

项目成果

Ichiyama K.: "A duodenally absorbable CXC chemokine receptor 4 antagonist, KRH-1636, exhibits a potent and selective anti-HIV-1 activity"Proc.Natl.Acad.Sci. USA. 100(7). 4185-4190 (2003)

Ichiyama K.：“一种十二指肠可吸收的 CXC 趋化因子受体 4 拮抗剂 KRH-1636，表现出有效且选择性的抗 HIV-1 活性”Proc.Natl.Acad.Sci。

Uranishi H. et al: "Involvement of the pro-oncoprotein TLS (Translocated in liposarcoma) in nuclear factor - kB p65-mediated transcription as a coactivator"J. Biol. Chem.. 276. 13395-13401 (2001)

Uranishi H. 等人：“原癌蛋白 TLS（在脂肪肉瘤中易位）参与核因子 - kB p65 介导的转录作为共激活剂”J.

Sakuragi J, Iwamoto A, Shioda T: "Dissociation of genomic dimerization from packaging functions and virion maturation of human immunodeficiecny virus type 1"Journal of Virology. 76. 959-967 (2002)

Sakuragi J、Iwamoto A、Shioda T：“基因组二聚化与 1 型人类免疫缺陷病毒的包装功能和病毒颗粒成熟的分离”病毒学杂志。

Hoshino Y, Nakata K, Hoshino S, Honda Y, Tse D, Shioda T, Rom W, Weiden M: "Maximal HIV-1 replication in alveolar macrophages during tuberculosis requires both lymphocyte contact and cytokines"Journal of Experimental. Medicine. (印刷中).

Hoshino Y、Nakata K、Hoshino S、Honda Y、Tse D、Shioda T、Rom W、Weiden M：“结核病期间肺泡巨噬细胞中的最大 HIV-1 复制需要淋巴细胞接触和细胞因子”《实验医学杂志》（印刷版）。期间）。

Takahashi K: "NMR analysis of intra- and inter-molecular stems in the dimerization initiation site of the HIV-1 genome"Journal of Biochemistry. 127. 681-686 (2000)

Takahashi K：“HIV-1 基因组二聚化起始位点的分子内和分子间干的核磁共振分析”生物化学杂志。